The present invention relates to novel ruthenium labeled transferrin compounds, methods for preparing and purifying them, and their uses in nuclear medicine as a diagnostic tool, as well as possible uses in the treatment of tumors and abscesses.
The prior art discloses the labeling of proteins with Technetium-99 (Tc-99) to produce an injectable isotopic tracer as described in U.S. Pat. No. 4,057,617; and the labeling with tritium is described in U.S. Pat. No. 4,162,142. The labeling of transferrin with Indium-113 (In-113) for purposes of measuring circulation and visualizing the placenta is described in U.S. Pat. No. 3,939,258. However, there is no disclosure of a ruthenium transferrin complex.
Even though short-lived radionuclides, in particular Tc-99m, have found extensive application in nuclear medicine, intermediate half-life nuclides may be extremely valuable for diagnostic studies at longer time intervals. Many nuclear medicine procedures indeed require delayed scanning or frequent imaging over a long time period in order to obtain diagnostically important information. Ruthenium-97 is an ideal nuclide for such applications; its potential in nuclear medicine was first suggested by Subramanian et al in 1970 (G. Subramanian, J. G. McAfee, and J. K. Poggenburg, Ru-97: Preliminary evaluation of a new radionuclide for use in nuclear medicine. J. Nucl. Med. 11:365 (1970) (Abstract)). The 2.9 day half-life and an essentially monoenergetic gamma emission (216 DeV, 86%), in conjunction with the chemical reactiveness of ruthenium provide an extremely useful combination. The 2.9 day half-life of Ruthenium-97 makes many studies and procedures possible, not otherwise practical with Technetium-99m. In many ways, the physical characteristics of Ru-97 are superior to those of Gallium-67 (Ga-67) and In-111.
Gallium-67 citrate is presently the most widely used agent for tumor localization. This agent has serious disadvantages, however. It does not concentrate selectively in tumors, the background remains high, and its imaging properties are far from ideal. As clinical trails have progressed, it has become evident that gallium-67 citrate concentrates in a variety of normal structures and in several diverse benign and malignant pathologic lesions. This lack of specificity has made the interpretation of gallium-67 scans difficult.